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BioequivalencePhase 1NCT04768985

Study to Assess the Bioequivalence of Acalabrutinib Tablet and Acalabrutinib Capsule

A Phase 1 study testing Treatment A: Acalabrutinib tablet and Treatment B: Acalabrutinib capsule in people with Bioequivalence, run by AstraZeneca at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study is a multicenter, Phase I, open-label, randomized, 2-sequence, 2-treatment, 2-period, crossover, bioequivalence study with single doses of acalabrutinib administered orally in healthy participants. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Bioequivalence
What is being tested?
Treatment A: Acalabrutinib tablet and Treatment B: Acalabrutinib capsule
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
3 sitesUnited States
Study dates
25 Feb 2021to 10 May 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • Females must have a negative pregnancy test at Screening and on admission to the study center, must not be lactating, and must be of non-childbearing potential, confirmed at Screening, by fulfilling protocol defined criteria
  • Have a body mass index between 18.5 and 30 kg/m^2 inclusive and weigh at least 50 kg and no more than 100 kg inclusive, at Screening
  • Non-smokers and those participants who have not smoked (including e cigarettes) or used nicotine products (cigarettes, pipes, cigars, chewing tobacco, nicotine patch, or any other nicotine containing products) within the 90 days prior to Screening
  • Calculated creatinine clearance (CrCl) ≥ 90 mL/min as determined by Cockcroft-Gault method (using actual body weight)
  • Males:
  • CrCl = Weight (kg) × (140 - Age)/72 × serum creatinine (mg/dL) in mL/min
  • Females:
  • CrCl = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL) in (mL/min)

Who cannot join

  • History or presence of any clinically significant disease (including active coronavirus disease 2019 [COVID-19] infection) or disorder
  • History or presence of gastrointestinal, hepatic, or renal disease, or any other condition known to interfere with absorption, distribution, metabolism, or excretion of drugs
  • Any clinically significant illness, medical/surgical procedure, or trauma within 30 days of the first administration of study drug
  • Any clinically significant abnormalities in hematology, coagulation, clinical chemistry, or urinalysis results, at Screening and prior to first dose, as judged by the Investigator and defined as:
  • Hemoglobin less than lower limit of normal (ii) Absolute neutrophils less than lower limit of normal (iii) Platelets less than lower limit of normal (iv) Serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase or serum bilirubin (total bilirubin and direct bilirubin) > upper limit of normal
  • Any clinically significant abnormal findings in vital signs at Screening or on Day 1 (eg, systolic BP < 90 mmHg or > 140 mmHg; diastolic BP < 50 mmHg or > 90 mmHg; pulse < 45 or > 90 bpm)
Show all 20Show fewer
  • Any clinically significant abnormalities on standard 12-lead ECG at Screening or on Day 1
  • Any positive result for HBsAg, hepatitis C antibody, and HIV testing, at Screening
  • Has received a new chemical entity (defined as a compound which has not been approved for marketing) within 90 days of the first administration of study drug in this study. The period of exclusion begins 90 days after the final dose or 30 days after the last visit whichever is the longest
  • History of severe allergy/hypersensitivity or ongoing allergy/hypersensitivity, or history of hypersensitivity to drugs with a similar chemical structure or class to acalabrutinib
  • Positive screen for drugs of abuse or cotinine and alcohol, at Screening and on admission to the study center
  • Treatment with prescription or non-prescription drugs or other products known to be strong CYP3A, P-gp, or breast cancer resistance protein (BCRP) inhibitors or substrates of BCRP or MATE1 (within 14 days before first administration of study drug or longer if the medication has a long half life) and strong CYP3A inducers (within 28 days before first administration of study drug or longer if the medication has a long half life)
  • Use of any prescribed or non prescribed medication including antacids, analgesics (other than paracetamol/acetaminophen), herbal remedies, megadose vitamins (intake of 20 to 600 times the recommended daily dose), and minerals during the 14 days prior to the first administration of study drug or longer if the medication has a long half life
  • Excessive intake of caffeine-containing drinks or food (eg, coffee, tea, chocolate) as judged by the Investigator
  • Inability to swallow acalabrutinib tablets or acalabrutinib capsules
  • Evidence of ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infections)
  • Participant has a positive test result for severe acute respiratory syndrome coronavirus 2 reverse transcriptase polymerase chain reaction before randomization
  • Participant has clinical signs and symptoms consistent with COVID-19, eg, fever, dry cough, dyspnea, sore throat, fatigue, or confirmed infection by appropriate laboratory test within the last 4 weeks prior to Screening or on admission
  • History of severe COVID-19 (hospitalization, extracorporeal membrane oxygenation, mechanically ventilated)
  • Participants who are regularly exposed to COVID-19 as part of their daily life (eg, health care professionals working in COVID-19 wards or at emergency departments)

Trial locations and contacts

3 sites in 1 country.

United States3 sites
  • Research Site

    Brooklyn, Maryland, 21225

  • Research Site

    Glendale, California, 91206

  • Research Site

    Salt Lake City, Utah, 84107

Other trials in United States

About this study

Official title: A Phase I, Open-Label, Randomized, 2-Treatment, 2-Period, Crossover Study in Healthy Subjects to Assess the Bioequivalence of Acalabrutinib Tablet and Acalabrutinib Capsule

This study is a multicenter, Phase I, open-label, randomized, 2-sequence, 2-treatment, 2-period, crossover, bioequivalence study with single doses of acalabrutinib administered orally in healthy participants. The study is designed to demonstrate the bioequivalence of acalabrutinib tablet (Treatment A) compared with marketed acalabrutinib capsule (Treatment B) in the fasted state.

Read the detailed description

Eligible healthy participants will be randomized to receive either treatment sequence 1 (AB) or treatment sequence 2 (BA), as follows:

  • Treatment A: Acalabrutinib tablet, 100 mg, fasted state
  • Treatment B: Acalabrutinib capsule, 100 mg, fasted state

Participants will receive fixed single doses of acalabrutinib on 2 occasions, under fasted conditions.

The study will comprise:

  • Visit 1: A screening period of up to 28 days before first dosing.
  • Visit 2: Two treatment periods:
  • Participants will be admitted to the study center on Day -2 of Treatment Period 1 to confirm eligibility before first dosing. Eligibility criteria will be reconfirmed on Day -1 of each treatment period.
  • On Day 1 of Treatment Periods 1 and 2, participants will be administered the assigned treatment (A or B) as randomized, followed by a protocol defined washout period between Treatment Periods 1 and 2.
  • Visit 3: A Follow-up Visit/Early Termination Visit at 7 to 10 days after last administration of study drug.

Each participant will be involved in the study for approximately 6 weeks.

Conditions
Bioequivalence
Being tested
Treatment A: Acalabrutinib tablet, Treatment B: Acalabrutinib capsule
Keywords
Pharmacokinetics, Healthy participants, Bruton tyrosine kinase, Acalabrutinib

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Treatment A: Acalabrutinib tabletDrug

    Also called CALQUENCE

    Participants will receive fixed single doses of acalabrutinib tablet in 2 treatment periods, under fasted conditions.

  • Treatment B: Acalabrutinib capsuleDrug

    Also called CALQUENCE

    Participants will receive fixed single doses of acalabrutinib capsule in 2 treatment periods, under fasted conditions.

Study groups in NCT04768985
Study groupRoleWhat they receive
Treatment sequence 1: Treatment ABExperimentalParticipants will be randomized to receive one of the two different treatment sequences. In each treatment sequence participant will receive fixed single doses of 100 mg acalabrutinib orally (Treatment A; Treatment B) in 2 treatment periods, under fasted conditions. Treatment A will include acalabrutinib tablet and Treatment B will include acalabrutinib capsule.
Receives: Drug: Treatment A: Acalabrutinib tablet; Drug: Treatment B: Acalabrutinib capsule
Treament sequence 2: Treatment BAExperimentalParticipants will be randomized to receive one of the two different treatment sequences. In each treatment sequence participant will receive fixed single doses of 100 mg acalabrutinib orally (Treatment B; Treatment A) in 2 treatment periods, under fasted conditions. Treatment A will include acalabrutinib tablet and Treatment B will include acalabrutinib capsule.
Receives: Drug: Treatment A: Acalabrutinib tablet; Drug: Treatment B: Acalabrutinib capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Area under plasma concentration time curve from zero to infinity (AUCinf) of Acalabrutinib

    To compare the AUCinf of acalabrutinib capsule with the tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  2. Area under the plasma concentration time curve from zero to the last quantifiable concentration (AUClast) of Acalabrutinib

    To compare the AUClast of acalabrutinib capsule with the tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  3. Maximum observed plasma (peak) drug concentration (Cmax) of Acalabrutinib

    To compare the Cmax of acalabrutinib capsule with the tablet

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

Secondary outcomes (10)
  1. Area under plasma concentration time curve from zero to infinity (AUCinf) of ACP-5862

    To compare the AUCinf of acalabrutinib capsule with the tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  2. Area under the plasma concentration time curve from zero to the last quantifiable concentration (AUClast) of ACP-5862

    To compare the AUClast of acalabrutinib capsule with the tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  3. Maximum observed plasma (peak) drug concentration (Cmax) of ACP-5862

    To compare the Cmax of acalabrutinib capsule with the tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  4. Time to reach peak or maximum concentration (tmax) following drug administration for acalabrutinib and ACP-5862

    To compare the tmax of acalabrutinib capsule with the acalabrutinib tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  5. Half life associated with terminal slope (λz) of a semi logarithmic concentration time curve (t½λz) for acalabrutinib and ACP-5862

    To compare the t½λz of acalabrutinib capsule with the acalabrutinib tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  6. Mean residence time of the unchanged drug in the systemic circulation from zero to infinity (MRT) for acalabrutinib and ACP-5862

    To compare the MRT of acalabrutinib capsule with the acalabrutinib tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  7. Terminal rate constant, estimated by log linear least squares regression of the terminal part of the concentration time curve (λz) for acalabrutinib and ACP-5862

    To compare the λz of acalabrutinib capsule with the acalabrutinib tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  8. Metabolite (ACP-5862) to parent (acalabrutinib) ratio based on AUCinf and/or AUClast (M:P[AUC])

    To compare the M:P[AUC] of acalabrutinib capsule with the tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  9. Metabolite (ACP-5862) to parent (acalabrutinib) ratio based on Cmax (M:P [Cmax])

    To compare the M:P[Cmax] of acalabrutinib capsule with the tablet.

    Measured: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose

  10. Number of participants with adverse events and serious adverse events

    Comparison of the safety and tolerability of single doses of acalabrutinib capsule with the tablet.

    Measured: From screening day (Day -28) until Follow-up/end of treatment visit (at 7 to 10 days after last study drug administration)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Feb 2021
  2. Study start25 Feb 2021
  3. Primary completion10 May 2021
  4. Study completion10 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Other
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04768985
Sponsor's protocol ID
D8223C00013
Status last verified
Mar 2022
First submitted
22 Feb 2021
Last updated
8 Jul 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Treatment A: Acalabrutinib tablet and Treatment B: Acalabrutinib capsule in people with Bioequivalence, run by AstraZeneca at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Area under plasma concentration time curve from zero to infinity (AUCinf) of Acalabrutinib (time frame: Pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 10, 12, 24, and 48 hours post-dose). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2022.

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